title: A novel mutation in PLP1 causes severe hereditary spastic paraplegia type 2.
abstract: Hereditary spastic paraplegia (HSP) type 2 is a proteolipid protein (PLP1)-related genetic disorder that is characterized by dysmyelination of the central nervous system resulting primarily in limb spasticity, cognitive impairment, nystagmus, and spastic urinary bladder of varying severity. Previously reported PLP1 mutations include duplications, point mutations, or whole gene deletions with a continuum of phenotypes ranging from severe Pelizaeus-Merzbacher disease (PMD) to uncomplicated HSP type 2. In this manuscript we report a novel PLP1 missense mutation (c.88G>C) in a family from Argentina. This mutation is in a highly conserved transmembrane domain of PLP1 and the mutant protein was found to be retained in the endoplasmic reticulum when expressed in vitro. Due to the variable expressivity that characterizes these disorders our report contributes to the knowledge of genotype-phenotype correlations of PLP1-related disorders.
authors.affiliation: Department of Pediatrics, University of Colorado Denver School of Medicine, USA; Human Medical Genetics and Genomics Program, University of Colorado Denver School of Medicine, USA.
authors.forename: Leila
authors.initials: L
authors.lastname: Noetzli
authors.forename: Pablo G
authors.initials: PG
authors.lastname: Sanz
authors.forename: Gary L
authors.initials: GL
authors.lastname: Brodsky
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Hinckley
authors.forename: Juan C
authors.initials: JC
authors.lastname: Giugni
authors.forename: Rolando J
authors.initials: RJ
authors.lastname: Giannaula
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzalez-Alegre
authors.forename: Jorge
authors.initials: J
authors.lastname: Di Paola
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
keywords: C; DM20; DNA; EGFP; ER; G; HSP; Hereditary spastic paraplegia; L1 cell adhesion molecule (human gene); L1CAM; MUT; NCBI; National Center for Biotechnology Information; Novel mutation; OMIM; Online Mendelian Inheritance in Man; PDI; PLP1; PMD; Pelizaeus–Merzbacher disease; Plp1; SPG1; UPR; WT; c.88G>C; c.89C>A; cDNA; cDNA nucleotide 88 is changed from guanosine to cytidine; cDNA nucleotide 89 is changed from cytidine to adenosine; complementary DNA; cytidine; deoxyribonucleic acid; endoplasmic reticulum; enhanced green fluorescent protein; guanosine; hereditary spastic paraplegia; isoform of PLP1; kb; kilobase; mutant; p.A30E; p.A30P; protein amino acid 30 is changed from alanine to glutamic acid; protein amino acid 30 is changed from alanine to proline; protein disulfide isomerase; proteolipid protein 1 (human gene); proteolipid protein 1 (human protein); proteolipid protein 1 (mouse gene); spastic paraplegia type 1; unfolded protein response; wild type